Abstract
Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a developmental
encephalopathy caused by pathogenic variants in the gene CDKL5. This unique disorder includes early infantile onset refractory epilepsy, hypotonia,
developmental intellectual and motor disabilities, and cortical visual impairment.
We review the clinical presentations and genetic variations in CDD based on a systematic
literature review and experience in the CDKL5 Centers of Excellence. We propose minimum
diagnostic criteria. Pathogenic variants include deletions, truncations, splice variants,
and missense variants. Pathogenic missense variants occur exclusively within the kinase
domain or affect splice sites. The CDKL5 protein is widely expressed in the brain,
predominantly in neurons, with roles in cell proliferation, neuronal migration, axonal
outgrowth, dendritic morphogenesis, and synapse development. The molecular biology
of CDD is revealing opportunities in precision therapy, with phase 2 and 3 clinical
trials underway or planned to assess disease specific and disease modifying treatments.
Keywords
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Article info
Publication history
Published online: February 22, 2019
Accepted:
February 16,
2019
Received:
January 6,
2019
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
